PROJECT SUMMARY The second Alagille Syndrome Scientific Meeting ? Connecting the Pieces will be held June 20- 21, 2019 at Cincinnati Children?s Hospital Medical Center (CCHMC). This will be the first time that this event is held in connection with the 8th International Symposium on ALGS, the Alagille Syndrome Alliance?s (ALGSA?s) signature family conference. This scientific meeting will provide an unmet need in the scientific and clinical community, both academic and industrial, by dedicating itself to the pleiotropic nature of ALGS and the potential context dependent regulatory mechanisms influencing Notch pathway activity. Mutations in Notch pathway components were found to be associated with greater than 95% of the patients with ALGS in 1997. Because ALGS is a disease of reduced Notch activity, the current targets to antagonize Notch activity will not benefit this patient population. The long-term goal is establishment of a forum to address the most important problems and opportunities for research and discovery to improve the outcome of patients with ALGS. The goal will be visualized by bringing together 1) clinicians that treat patients with ALGS, 2) investigators that focus on mechanistic aspects of Notch signaling, 3) investigators that focus on mechanistic aspects of organ development and pathogenesis of tissues and organs with defects identified in patients with ALGS, 4) industrial partners interested in the rare disease space, and 5) patients with ALGS, families, and patient advocates. Our goal is to disseminate cutting edge information to patients, advocates, clinicians, and scientists both academic and industrial ? ?Connecting the Pieces?. The Specific Aims for this interdisciplinary yet syndrome-focused meeting is to bring together a diverse community of 150 clinicians and scientists engaged in the care of patients with ALGS and discovery of possible avenues to new, safer and more effective way to manipulate Notch signaling in disease, development and regeneration related to ALGS. The 21 invited speakers and 6 moderators represent world leaders with vast knowledge and cutting edge discoveries in their respective fields. This will provide education to everyone and stimulate development of young investigators. Significantly, the environment and time set aside for formal and informal discussions, will generate a forum in which cutting edge technologies, ideas and discoveries can be freely exchanged, stimulating new ideas. Most importantly, this forum will provide the opportunity for scientists, patients with ALGS and their families to interact and learn from each other.